Femtonewton Forces Can Control Protein-Meditated DNA Looping

TL;DR

This study demonstrates that extremely small forces, around 100 femtonewtons, can significantly influence DNA looping mediated by proteins, affecting gene regulation processes.

Contribution

It provides the first quantitative evidence that femtonewton forces can control protein-mediated DNA looping, supported by experimental data and polymer modeling.

Findings

A 200 fN tension reduces DNA loop formation rate tenfold.

Once formed, DNA loops are insensitive to applied force.

Polymer model aligns with experimental observations.

Abstract

We show that minuscule entropic forces, on the order of 100 fN, can prevent the formation of DNA loops--a ubiquitous means of regulating the expression of genes. We observe a tenfold decrease in the rate of LacI-mediated DNA loop formation when a tension of 200 fN is applied to the substrate DNA, biasing the thermal fluctuations that drive loop formation and breakdown events. Conversely, once looped, the DNA-protein complex is insensitive to applied force. Our measurements are in excellent agreement with a simple polymer model of loop formation in DNA, and show that an anti-parallel topology is the preferred LacI-DNA loop conformation for a generic loop-forming construct.